3S0Z

Crystal structure of New Delhi Metallo-beta-lactamase (NDM-1)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.236 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

A structural view of the antibiotic degradation enzyme NDM-1 from a superbug.

Guo, Y.Wang, J.Niu, G.Shui, W.Sun, Y.Zhou, H.Zhang, Y.Yang, C.Lou, Z.Rao, Z.

(2011) Protein Cell 

  • DOI: https://doi.org/10.1007/s13238-011-1055-9
  • Primary Citation of Related Structures:  
    3S0Z

  • PubMed Abstract: 

    Gram-negative Enterobacteriaceae with resistance to carbapenem conferred by New Delhi metallo-β-lactamase 1 (NDM-1) are a type of newly discovered antibioticresistant bacteria. The rapid pandemic spread of NDM-1 bacteria worldwide (spreading to India, Pakistan, Europe, America, and Chinese Taiwan) in less than 2 months characterizes these microbes as a potentially major global health problem. The drug resistance of NDM-1 bacteria is largely due to plasmids containing the blaNDM-1 gene shuttling through bacterial populations. The NDM-1 enzyme encoded by the blaNDM-1 gene hydrolyzes β-lactam antibiotics, allowing the bacteria to escape the action of antibiotics. Although the biological functions and structural features of NDM-1 have been proposed according to results from functional and structural investigation of its homologues, the precise molecular characteristics and mechanism of action of NDM-1 have not been clarified. Here, we report the three-dimensional structure of NDM-1 with two catalytic zinc ions in its active site. Biological and mass spectroscopy results revealed that D-captopril can effectively inhibit the enzymatic activity of NDM-1 by binding to its active site with high binding affinity. The unique features concerning the primary sequence and structural conformation of the active site distinguish NDM-1 from other reported metallo-β-lactamases (MBLs) and implicate its role in wide spectrum drug resistance. We also discuss the molecular mechanism of NDM-1 action and its essential role in the pandemic of drug-resistant NDM-1 bacteria. Our results will provide helpful information for future drug discovery targeting drug resistance caused by NDM-1 and related metallo-β-lactamases.


  • Organizational Affiliation

    High-throughput Molecular Drug Discovery Center, Tianjin Joint Academy of Biotechnology and Medicine, Tianjin, China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Metallo-beta-lactamase
A, B
224Escherichia coliMutation(s): 0 
Gene Names: blaNDM-1
UniProt
Find proteins for E5KIY2 (Escherichia coli)
Explore E5KIY2 
Go to UniProtKB:  E5KIY2
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupE5KIY2
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.267 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.236 
  • Space Group: P 31
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 40.696α = 90
b = 40.696β = 90
c = 215.292γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2023-11-01
    Changes: Data collection, Database references, Derived calculations, Refinement description